Hepatic stellate cells (HSCs) play a critical role in the fibrogenesis of liver, so they are the target cells of antifibrotic therapy. There is an increasing need for safe and effective nonviral gene delivery systems. Here, we report that gene transfer and transfection efficiency in HSC-T6 can be enhanced by the use of a novel poly(ethyleneimine) biscarbamate conjugate (PEIC) with a low molecular weight. When added to a DNA solution, PEIC condensed DNA at a w/w ratio above 1 to15 form 153 to 247 nm polyplexes with -1.18 to 22.86 mV in zeta potential. PEIC was able to effectively protect condensed DNA from DNase I degradation. Our results showed that the uptake of plasmid DNA by HSC-T6 cells depended on the N/P ratios. Treatment with PEIC at an N/P ratio of 7/1 was most effective, increasing the uptake of plasmid DNA in HSC-T6 cells by 4.5 -fold relative to PEI (branched 25 kDa), 45-fold relative to Lipofectamine 2000, and 20-fold relative to FuGENE™6 , respectively. Collectively, these results indicate that PEIC at the optimal N/P ratio might be used to safely enhance gene delivery and transfection of HSC-T6.

Key words: Poly (ethylene imine) biscarbamate conjugate (PEIC), transfection; cytotoxicity, gene delivery, hepatic stellate cells.